The introduction of immunotherapy, either as monotherapy or in combination with tyrosine kinase inhibitors (TKIs), has profoundly reshaped the first-line treatment of metastatic renal cell carcinoma. Nevertheless, most patients eventually experience disease progression, highlighting the unmet clinical need for effective therapeutic strategies in the post-immunotherapy setting. Cabozantinib, a multikinase TKI targeting VEGFR, MET, and AXL, represents one of the most established treatment options in this context. This mini-review summarizes the biological rationale, key clinical evidence, and the most recent data presented at major international congresses, with a specific focus on the positioning of cabozantinib after failure of immunotherapy-based regimens or immune-TKI combinations. • Cabozantinib is a key option after immunotherapy failure in metastatic RCC. • VEGFR, MET and AXL inhibition targets resistance and tumor microenvironment. • Prospective and real-world studies confirm post-immunotherapy efficacy. • CONTACT-03 shows no benefit from adding immunotherapy to cabozantinib. • Patient selection and proactive toxicity management optimize outcomes.
Catalano et al. (Wed,) studied this question.